Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 209, Issue 6, Pages 1091-1103Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20112655
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Funding
- European Commission
- Bill and Melinda Gates Foundation as part of the Collaboration for AIDS Vaccine Discovery (CAVD) [38637, 38619]
- UK Medical Research Council
- Medical Research Council [MC_EX_G0800785, G0801176] Funding Source: researchfish
- MRC [MC_EX_G0800785, G0801176] Funding Source: UKRI
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Llamas (Lama glama) naturally produce heavy chain-only antibodies (Abs) in addition to conventional Abs. The variable regions (VHH) in these heavy chain-only Abs demonstrate comparable affinity and specificity for antigens to conventional immunoglobulins despite their much smaller size. To date, immunizations in humans and animal models have yielded only Abs with limited ability to neutralize HIV-1. In this study, a VHH phagemid library generated from a llama that was multiply immunized with recombinant trimeric HIV-1 envelope proteins (Envs) was screened directly for HIV-1 neutralization. One VHH, L8CJ3 (J3), neutralized 96 of 100 tested HIV-1 strains, encompassing subtypes A, B, C, D, BC, AE, AG, AC, ACD, CD, and G. J3 also potently neutralized chimeric simian-HIV strains with HIV subtypes B and C Env. The sequence of J3 is highly divergent from previous anti-HIV-1 VHH and its own germline sequence. J3 achieves broad and potent neutralization of HIV-1 via interaction with the CD4-binding site of HIV-1 Env. This study may represent a new benchmark for immunogens to be included in B cell-based vaccines and supports the development of VHH as anti-HIV-1 microbicides.
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